Hepatitis C Virus–Specific Immune Responses and Quasi-Species Variability at Baseline Are Associated with Nonresponse to Antiviral Therapy during Advanced Hepatitis C

Pretreatment hepatitis C virus (HCV)–specific lymphoproliferative (LP) responses, neutralizing antibody (NA) responses, intrahepatic cytotoxic T lymphocyte (CTL) responses, and HCV quasi-species (QS) diversity and complexity were examined in patients with advanced hepatic fibrosis (Ishak fibrosis sc...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of infectious diseases 2006-04, Vol.193 (7), p.931-940
Main Authors: Morishima, Chihiro, Polyak, Stephen J, Ray, Ranjit, Doherty, Michael C, Di Bisceglie, Adrian M, Malet, Peter F, Bonkovsky, Herbert L, Sullivan, Daniel G, Gretch, David R, Rothman, Alan L, Koziel, Margaret James, Lindsay, Karen L
Format: Article
Language:English
Subjects:
Adult
Antibodies, Viral - blood
Antiviral Agents - administration & dosage
Antiviral Agents - pharmacology
Antiviral Agents - therapeutic use
Drug Resistance, Viral
Drug Therapy, Combination
Female
Genetic Variation
Hepacivirus - classification
Hepacivirus - genetics
Hepacivirus - immunology
Hepatitis C
Hepatitis C - drug therapy
Hepatitis C - immunology
Hepatitis C - virology
Hepatitis C virus
Humans
Interferon-alpha - administration & dosage
Interferon-alpha - pharmacology
Interferon-alpha - therapeutic use
Liver - pathology
Middle Aged
Neutralization Tests
Polyethylene Glycols - administration & dosage
Polyethylene Glycols - pharmacology
Polyethylene Glycols - therapeutic use
Recombinant Proteins
Ribavirin - administration & dosage
Ribavirin - pharmacology
Ribavirin - therapeutic use
T-Lymphocytes - immunology
T-Lymphocytes, Cytotoxic - immunology
Treatment Outcome
Citations: Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Pretreatment hepatitis C virus (HCV)–specific lymphoproliferative (LP) responses, neutralizing antibody (NA) responses, intrahepatic cytotoxic T lymphocyte (CTL) responses, and HCV quasi-species (QS) diversity and complexity were examined in patients with advanced hepatic fibrosis (Ishak fibrosis score of ⩾3) and prior nonresponse to interferon (IFN)–α therapy who were enrolled in the initial phase of the Hepatitis C Antiviral Long-Term Treatment against Cirrhosis Trial. Positive baseline HCV E1– and/or E2–specific NA responses (P=.01) and higher baseline HCV QS diversity (P=.01) were more commonly found in patients who did not become sustained virologic responders (SVRs) at week 72 (W72) than they were in those who did. No patients with positive results for both the LP and NA assays achieved a sustained virologic response. Multiple logistic regression analysis revealed that, when the presence of cirrhosis, prior ribavirin therapy, genotype 1 infection, log serum HCV RNA level, and receipt of >80% of the prescribed medication were controlled for, a sustained virologic response (W72) was negatively correlated with positive baseline LP assay results (P=.02) and with 1 or more positive assays (LP, NA, or CTL) (P=.02). No differences were noted in baseline intrahepatic CTL activity between SVRs and non-SVRs. Thus, in patients with advanced hepatic fibrosis due to HCV infection, pretreatment HCV-specific immune responses and increased QS variability appear to hinder viral clearance by pegylated IFN-α2a and ribavirin combination therapy
ISSN:0022-1899
1537-6613
DOI:10.1086/500952